Evolutionary forces are known to drive the fixation of locally adaptive genetic variation within populations, and such variation is thought to be involved in the differential response to disease and pharmacological agents observed in human populations. Natural variation is well documented in plants, and plants provide an excellent model for investigations into its genetic origins, maintenance and adaptive significance. We aim to take advantage of the natural genetic variation that occurs between populations of the genetic model plant Arabidopsis thaliana (Arabidopsis) to identify gene functions that vary between these natural populations. Such a set of polymorphic genes and gene functions will provide the essential tools required to uncover the genetic mechanisms that drive the fixation of locally adaptive genetic variation within a population. To link natural genetic variation to function, we have applied our high-throughput Inductively Coupled Plasma - Mass Spectroscopy (ICP-MS) based elemental-profiling platform, in combination with genome-wide association mapping and traditional linkage mapping, to a genotyped panel of 360 Arabidopsis accessions, Recombinant Inbred Lines (RILs) and F2 populations. Such a system has started to reveal the identification of loci that drive the natural variation we observe in the plant's elemental-profile or "ionome" including P, Ca, K, Mg (macronutrients);Cu, Fe, Zn, Mn, Co, Ni, Se, Mo, I (micronutrients of significance to plant and human health);Na, As, and Cd (minerals causing agricultural or environmental problems). We have demonstrated the value of such studies by identifying naturally occurring alleles of several genes in A. thaliana that function to control shoot levels of various elements, including Na, Co, Mo and Zn. Further studies are proposed to continue the discovery of naturally polymorphic ionomic loci, and also to uncover the function of these ionomic loci along with their underlying causal genetic and epigenetic basis. Sequence analysis of the haplotypes of such loci across the large panel of A. thaliana populations has identified evidence of recent directional selection due to local adaptation, and further experiments are proposed to determine the functional basis and evolutionary significance of this selection. Such information will help shed light on the evolutionary processes involved in adaptation of organisms to local environments, to understanding ion homeostasis networks, and will have applications to improving the mineral content of food crops for improved human health. After all, plants provide the major source of nutrition for a large portion of the world's population. PUBLIC HEALTH RELEVANCE: Mineral nutrient deficiencies, such as iron and zinc, remain worldwide health concerns. Biofortification of food crops based on our research offers a sustainable, low-cost solution to this problem. Indeed, biofortification was recently ranked in the top 10 biotechnologies for improving health in developing countries.